Abstract: Screening and antiviral prophylaxis for hepatitis B virus (HBV) reactivation has become well established for patients receiving rituximab-based chemotherapy and hematopoietic stem cell transplants. Chemotherapy regimens for solid tumors also pose a risk for HBV reactivation, but screening and prophylaxis for this population remains controversial because of varying reactivation rates and ... read moreinsufficient evidence. Consequently, there is a need to synthesize and compare the existing data. The aim of the current study is to perform a systematic review and meta-analysis to determine HBV reactivation rates across common chemotherapy regimens for solid and hematologic malignancies. Studies through October 1, 2014 that examined HBV reactivation in patients receiving chemotherapy were collected from MEDLINE, PubMed, Web of Science, Cochrane Central Register of Controlled Trials, TOXNET, and Scopus. Inclusion criteria included patients with HBV undergoing chemotherapy for all solid tumors, hematological diseases, and bone marrow transplantation. The primary outcome was HBV reactivation defined as an increase in HBV DNA levels from baseline or the re-emergence of surface antigen when previously surface antigen negative. Risk of reactivation and odds ratio (OR) for prophylaxis used were estimated with random-effects models. Heterogeneity was assessed with Q and I2 statistics. A total of 1,706 articles were identified though database searches, of which 82 original reports were included in the current meta-analysis: 13 studies included only solid tumors (12 chronic infection, 1 past infection); 42 studies involved hematological malignancies (19 chronic infection, 13 past infection, 10 mixed chronic and resolved HBV); 8 studies included both solid and liquid tumors (7 chronic infection, 1 past infection); 18 studies involved hematopoietic stem cell transplant (HSCT) (8 chronic infection, 9 past infection, 1 chronic and past infection); and 1 study included patients with past infection with liquid tumors undergoing chemotherapy or HSCT. Solid tumors included cancers of the gastrointestinal tract, breast, lung, head and neck while liquid tumors were mostly lymphoma and leukemia. The risk of HBV reactivation in the absence of prophylaxis was highest in patients with chronic HBV and liquid tumors (51%) or receiving HSCT (54%) and lowest in patients with resolved HBV with hematological malignancies (5.8%). Those with solid tumors and chronic infection had a 24% risk of HBV reactivation, which is slightly higher than the risk seen in patients with resolved HBV receiving HSCT (19%). All analyses had significant heterogeneity. The addition of anti-viral prophylaxis reduced the risk of HBV reactivation across all categories. The presence of surface antibody also protected patients with a history of resolved infection from HBV reactivation for both liquid tumors (OR 0.19, 95% CI 0.09 - 0.39, p<0.001) and HSCT (OR 0.09, 95% CI 0.02 - 0.33, p<0.001). HBV reactivation occurs in patients with chronic HBV receiving solid tumor chemotherapy at rates comparable to other types of immunosuppressive therapy. This patient population merits HBV screening and antiviral prophylaxis prior to initiation of chemotherapy. Future studies evaluating the cost-effectiveness of universal screening are warranted. read less